Based on data from three studies with complete recording of adverse events in about 12,000 patients each, we determined that angioedema in association with the angiotensin converting-enzyme inhibitor enalapril maleate occurred during the first week of therapy at the rate of one case per 3000 patients per week. Thereafter, the incidence was 14-fold lower, without evidence of a temporal trend in incidence beyond the first week of therapy. The cumulative incidence was one case per 1000 patients treated (0.1%). An additional 138 case reports consistent with the diagnosis of angioedema were obtained from our overall controlled and marketed experience using enalapril in more than 1.2 million patients. These reports were examined to further characterize the reaction. The cases generally were mild, and they resolved on discontinuation of drug therapy. Seven patients experienced angioedema or urticaria in association with both enalapril and captopril, a structurally different angiotensin converting-enzyme inhibitor. This further suggested that the side effect is mechanism based. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be interrupted promptly, respiratory distress should be treated appropriately, and subsequent therapy should be initiated with an agent from an alternative class of medication.

In this health maintenance organization population, results with the use of the simplest approach, the last BP measurement recorded, were similar to results with the mean BP. Our findings indicate that evaluation of BP control in a large health maintenance organization will find substantial room for improvement, and clinicians should be encouraged to be more aggressive in their management of hypertension, especially with regard to the systolic BP, which until recent years has been underemphasized.

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PM101 is a new formulation of A-IV that is stable in commonly used infusion materials and avoids co-solvent related toxicities.

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Patients diagnosed as hypertensive have a high complaint rate, both on and off treatment and this has been postulated to be due to either their disease process, their being labelled as hypertensive, or to their treatment. Data from 6637 hypertensive patients being entered into clinical trials in general practice have been analysed to determine the relationship between the patient's age, sex, concurrent illnesses, concurrent medication, whether they were on antihypertensive treatment and the frequency of their reporting symptoms. The analysis was conducted using a multivariate technique. The frequency of reporting symptoms was greater in females than males. Those receiving antihypertensive therapy reported more symptoms than those who were not. This was notable with those receiving a beta‐adrenoceptor blocker (47% of such patients complaining). Patients receiving concurrent medication were more likely to report a symptom than those not (48 compared to 37%). This was particularly noticeable if central nervous system‐acting drugs were prescribed where the prevalence of symptoms was 52%. Patients already on antihypertensive treatment were more likely to be taking other medication for other conditions (37 vs 31%) than those not receiving antihypertensive treatment. Females were more likely to be taking other tablets than males (38 compared to 30%). The only symptoms which were less prevalent in those receiving treatment were headache, dizziness and breathlessness. All other symptoms were increased or unchanged in patients on antihypertensive therapy. This study indicates that present treatment for hypertension produces a high complaint rate from patients and that, when patients so complain, the possibility of their symptoms being due to their concurrent medication should be considered.

1. PM103 is an intravenous formulation of clopidogrel being developed as an alternative to oral clopidogrel to provide for dosing flexibility in the emergent clinical setting. The present first-in-human study assessed the pharmacokinetic and pharmacodynamic effects of PM103 and its safety in 144 healthy human subjects. 2. The present was a randomized open-label parallel-group trial. Single intravenous doses of PM103 (0.1, 1.0, 10, 30, 100 or 300 mg) were administered to each group (n = 24 subjects per group). Platelet aggregation was assessed at baseline and then 15 and 30 min and 2, 5 and 24 h after drug administration. Determination of plasma concentrations of clopidogrel, clopidogrel carboxylic acid metabolite and the clopidogrel thiol metabolite were assessed at baseline and at 1, 5, 10, 20 and 30 min and 1, 2, 3, 4, 6, 8, 12 and 24 h after drug administration. 3. PM103 produced a rapid, persistent and dose-related inhibition of platelet aggregation. The onset of the ant platelet effect paralleled the appearance in plasma of the clopidogrel thiol active metabolite. PM103 was well tolerated and no subjects discontinued treatment because of adverse events. 4. These data suggest that PM103 may be a suitable alternative to oral clopidogrel for patients in whom the desired clinical management would include administration of clopidogrel after coronary angiography but prior to percutaneous coronary intervention.